Original contributionsThe bronchopulmonary pathology of alpha-1 antitrypsin (AAT) deficiency: Findings of the death review committee of the national registry for individuals with severe deficiency of alpha-1 antitrypsin☆
Section snippets
Patients and methods
Of the 1129 Registry enrollees, 204 (18.1%) had died by the end of the Registry follow-up. Medical records were available for 120 decedents (59%). Autopsies were performed in 38 (32%) decedents, and slides were reviewed in 34 cases (89%). Twenty-five (21%) of the 120 subjects underwent lung transplantation, and slides of the native lung explants were reviewed in 23 cases (92%). A nonblinded reviewer (J.F.T.) reviewed histological slides of native lung tissue from 42 participants, who compose
Patient population and causes of death
Demographic and clinical features of the 42 patients are presented in Table 1. All patients had severe emphysema due to AAT deficiency as determined by clinical parameters, chest x-rays, and pulmonary function tests. The underlying and immediate causes of death as determined by the DRC are listed in Table 2.
Emphysema
All lungs were affected by severe panacinar emphysema, with a mean emphysema score of 7.9 ± 1.06 FIGURE 1, FIGURE 2. Focal centriacinar emphysema was observed infrequently. The
Discussion
The present study of native lungs from individuals with severe AAT deficiency confirms previous observations based on small series or individual patients.3, 4, 5, 6, 7, 8, 9, 10, 11, 12 The main findings from the current study are as follows:
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Panacinar emphysema was a universal feature of the lungs examined in this series.
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The emphysema (Nagai) score did not correlate with measurements of the diffusing capacity, percent predicted FVC, or percent predicted FEV-1.
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Bronchiectasis was an uncommon
Acknowledgements
The authors thank Dr. Joanne Wright for providing the poster used for grading small airways, and Ms. Susan Sherer for support in data collection and analysis.
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Small airways disease in patients with alpha-1 antitrypsin deficiency
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2021, Advanced Drug Delivery ReviewsCitation Excerpt :The classical clinical presentation of AATD-associated lung disease is severe whole-lung panacinar and lower lobe-predominant emphysema [59]. Although AATD shares many similar clinical characteristics with emphysema, the pathology features of AATD fundamentally differ from common emphysema [60]. Patients with AATD can also progress into COPD, which is often triggered by interactions between environmental and genetic factors [61].
Diagnostic evaluation of bronchiectasis
2019, Respiratory Medicine: XCitation Excerpt :In a study of over 200 bronchiectasis patients, the frequency of abnormal AAT genotypes was not significantly different than those without bronchiectasis [38]. In contrast, others have found an association between frank AAT deficiency and bronchiectasis [39–42]. Guest and Hansell [39] examined the CT scans in 17 patients with proven AAT deficiency and found that 7 of the patients had bronchial wall thickening and/or dilatation and one had gross cystic bronchiectasis.
Emphysema and Diseases of Large Airways
2018, Pulmonary Pathology: A Volume in the Series: Foundations in Diagnostic PathologyAlpha-1-antitrypsin deficiency: Genetic variations, clinical manifestations and therapeutic interventions
2017, Mutation Research - Reviews in Mutation ResearchCitation Excerpt :Carriers with the MZ alleles, however, may have an increased risk for lung disease, particularly if they smoke. AATD can lead to lung disease (emphysema and bronchiectasis) [67] liver disease (chronic hepatitis, cirrhosis and hepatoma) [27] and skin diseases (Panniculitis) [68]. However the major clinical manifestations are in the form of lung and liver disease, there are some other diseases associated with AATD but are very rare (Vasculitis, glomerulonephritis and celiac disease) [69], intracranial and intra-abdominal aneurysms [70], fibromuscular dysplasia [71] and pancreatitis [72].
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Supported by a grant (NO1-HR-86036) from the National Heart, Lung, and Blood Institute, National Institutes of Health.